Camptothecin derivatives are DNA-topoisomerase I inhibitors that have emerged as a prominent class of anticancer agents. Together with the taxanes, the topoisomerase I inhibitors are presumably the most important new class of anticancer drugs introduced into clinical practice. Pre-clinical studies demonstrated significant in vitro and in vivo activity of topoisomerase I inhibitors, such as camptothecin and its derivatives, on a broad range of tumors. The results from clinical trials were promising, as shown by the registration of two topoisomerase inhibitors, topotecan and irinotecan (also known as CPT-11), in many European countries and in the USA, for treatment of patients with ovarian and colorectal cancer, respectively. Other derivatives are currently at different stages of clinical development.
In patent application EP1044977 and in J. Med. Chem. 2001, 44, 3264-3274, camptothecin derivatives are described which bear an alkyloxime O-substituted at position 7 and which are endowed with antitumor activity higher than the compound of reference topotecan. Moreover these camptothecin derivatives bearing an imino group on position 7, also show an improved therapeutic index. Among these compounds one of the preferred molecules was shown to be 7-t-butoxyiminomethylcamptothecin (CPT 184, also known as ST1481 orgimatecan).
One of the main limitations of tumor therapies available today is the resistance of some kind of tumors to chemotherapy treatment (including camptothecin treatment). Moreover, despite of preliminary promising results, it is very difficult to find a drug, which is able to treat successfully different kinds of tumors.